Tag: amino acids

Less of a Specific Amino Acid Extends Lifespan and Health in Mice

Photo by Jose Ignacio Pompe on Unsplash

New research in mice has demonstrated that not having too much of a certain amino acid – present in many foods commonly eaten by overweight or obese individuals – extends their lifespan and reduces the incidence of diseases such as cancers.

“We like to say a calorie is not just a calorie,” says Dudley Lamming, a professor and metabolism researcher at the University of Wisconsin School of Medicine and Public Health. “Different components of your diet have value and impact beyond their function as a calorie, and we’ve been digging in on one component that many people may be eating too much of.”

Lamming is the lead author of a new study in mice, published recently in the journal Cell Metabolism showing that cutting down the amount of a single amino acid called isoleucine can, among other benefits, extend their lifespan, make them leaner and less frail as they age and reduce cancer and prostate problems, all while the mice ate more calories.

Amino acids are the molecular building blocks of proteins, and Lamming and his colleagues are interested in their connection to healthy aging.

In earlier research, data from UW–Madison’s Survey of the Health of Wisconsin showed the scientists that Wisconsinites with higher body mass index measurements tend to consume more isoleucine, an essential amino acid. Isoleucine is plentiful in foods including eggs, dairy, soy protein and many kinds of meat.

To better understand its health effects, Lamming and collaborators from across disciplines at UW–Madison fed genetically diverse mice either a balanced control diet, a version of the balanced diet that was low in a group of about 20 amino acids, or a diet formulated to cut out two-thirds of the diet’s isoleucine. The mice, which began the study at about six months of age (equivalent to a 30-year-old person) got to eat as much as they wanted.

“Very quickly, we saw the mice on the reduced isoleucine diet lose adiposity – their bodies got leaner, they lost fat,” says Lamming, while the bodies of the mice on the low-amino-acid diet also got leaner to start, but eventually regained weight and fat.

Mice on the low-isoleucine diet lived longer – on average 33% longer for males and 7% longer for females. And, based on 26 measures of health, including assessments ranging from muscle strength and endurance to tail use and even hair loss, the low-isoleucine mice were in much better shape during their extended lives.

“Previous research has shown lifespan increase with low-calorie and low-protein or low-amino-acid diets starting in very young mice,” says Lamming, whose work is supported by the National Institutes of Health. “We started with mice that were already getting older. It’s interesting and encouraging to think a dietary change could still make such a big difference in lifespan and what we call ‘healthspan,’ even when it started closer to mid-life.”

The mice on the low-isoleucine diets chowed down, eating significantly more calories than their study counterparts – probably to try to make up for getting less isoleucine, according to Lamming. But they also burned far more calories, losing and then maintaining leaner body weights simply through adjustments in metabolism, not by getting more exercise.

At the same time, Lamming says, they maintained steadier blood sugar levels and male mice experienced less age-related prostate enlargement. And while cancer is the leading cause of death for the diverse strain of mice in the study, the low-isoleucine males were less likely to develop a tumour.

Dietary amino acids are linked to a gene called mTOR that appears to be a lever on the aging process in mice and other animals as well as to a hormone that manages the body’s response to cold and has been considered a potential diabetes drug candidate for human patients. But the mechanism behind the stark benefits of low-isoleucine intake is not well understood. Lamming thinks the new study’s results may help future research pick apart causes.

“That we see less benefit for female mice than male mice is something we may be able to use to get to that mechanism,” he says.

While the results are promising, humans do need isoleucine to live, and reducing isoleucine from a diet that hasn’t been preformulated by a mouse chow company is not an easy task.

“We can’t just switch everyone to a low-isoleucine diet,” Lamming says. “But narrowing these benefits down to a single amino acid gets us closer to understanding the biological processes and maybe potential interventions for humans, like an isoleucine-blocking drug.”

The Survey of the Health of Wisconsin showed that people vary in isoleucine intake, with leaner participants tending to eat a diet lower in isoleucine. Other data from Lamming’s lab suggest that overweight and obese Americans may be eating significantly more isoleucine than they need.

“It could be that by choosing healthier foods and healthier eating in general, we might be able to lower isoleucine enough to make a difference,” Lamming says.

Source: University of Wisconsin-Madison

Amino Acid Supplementation after Fracture Surgery Reduces Complications

Lower leg bones
Photo by Nino Liverani on Unsplash

By adding conditionally essential amino acids (CEAA) to the diets of patients recovering from fracture fixation surgery, complications are reduced and skeletal muscle wasting is prevented, concludes a study published in The Journal of Bone & Joint Surgery.

The study supports the use of widely available CEAA supplements to promote recovery and preserve function in patients undergoing surgery for repair of major fractures. “Our results suggest that this inexpensive, low-risk intervention has considerable potential to improve outcomes after fracture fixation,” according to the report by Michael Willey, MD, and colleagues of University of Iowa Hospital and Clinics, Iowa City.

The study included 400 patients undergoing operative fixation of fractures in the limbs and/or pelvis at the researchers’ trauma centre. In equal numbers and stratified by fracture severity, patients were randomises to either standard postoperative nutrition or standard nutrition plus CEAA supplementation.

CEAAs are termed “conditionally essential” because the body doesn’t usually require them. However, during times of illness or stress, the need for these conditional amino acids increases dramatically. Previous studies have reported that CEAA supplementation can improve wound-healing and other outcomes in patients with a variety of conditions, including postoperative recovery. In the new trial, patients assigned to the CEAA group received a standard supplement that included arginine, leucine, and glutamine.

At follow-up, the overall complication rate was significantly lower for patients who received CEAA supplementation (30.5%) compared with those who did not receive CEAA (43.8%). The CEAA group also had a lower rate of nonunion (5.1 vs 13.2%, respectively). Some other types of complications, including surgical-site infections, were similar between groups.

Patients who undergo operative fracture fixation are at risk of skeletal muscle wasting, which often results in weight loss as a result of reduced muscle mass. In the new study, patients receiving CEAA supplements had little or no change in fat-free body mass. In contrast, patients receiving standard nutrition had a 1kg reduction in fat-free mass at 6 weeks postoperatively, which took until 12 weeks to return to normal.

An unexpected finding was a sharply reduced mortality rate in the CEAA group (0.5% compared to 4.1 % for the control). Although the authors could not explain the lower risk of death in patients receiving CEAA, they suggest it might result from “unidentified confounding factors.”

Despite advances in surgical techniques, trauma patients undergoing operative fixation of extremity and pelvic fractures remain at risk of complications and prolonged loss of function. “Malnutrition is a potentially modifiable risk factor for mortality, fracture nonunion, wound complications, and increased length of stay,” the authors wrote.

CEAA supplementation therefore appears to be a simple, risk-free, and inexpensive means of promoting good nutrition after fracture fixation surgery. Controlling for other factors, the relative risk of complications is about 40% lower in patients receiving CEAA, with no reduction in fat-free mass during the early weeks of recovery. The researchers concluded: “This study will serve as the foundation for multicentre [randomised controlled trials] that are designed to assess the impact of CEAA nutrition supplementation in reducing complications and loss of functional muscle mass in high-risk populations.”

Source: EurekAlert!